bims-oxygme Biomed News
on Oxygen metabolism
Issue of 2024–12–01
eight papers selected by
Onurkan Karabulut, Berkeley City College
  1. Sex Differences in Cardiac Tolerance to Oxygen Deprivation - 40 Years of Cardiovascular Research.
  2. Metabolic alterations of endothelial cells under transient and persistent hypoxia: study using a 3D microvessels-on-chip model.
  3. Effects of a Combined Method of Normobaric Hypoxia on the Repeated Sprint Ability Performance of a Nine-Time World Champion Triathlete: A Case Report.
  4. Ginsenoside Rg1 Prevents and Treats Acute Pulmonary Injury Induced by High-Altitude Hypoxia.
  5. From Hypoxia to Buoyancy: Serotonin and Oxygen Deprivation Rewire Neutrophils.
  6. Hypoxia-related bioinformatic signatures associated with prognosis and tumor microenvironment of pancreatic cancer: Current status, concerns, and future perspectives.
  7. Supplemental Oxygen on the Annie Smith Peck Expedition of 1903 to 6,367 m (20,892 ft) Mount Sorata (Illampu).
  8. Genomic Insights into Tibetan Sheep Adaptation to Different Altitude Environments.
  1. Physiol Res. 2024 Nov 29. 73(S2): S511-S525
    Sex Differences in Cardiac Tolerance to Oxygen Deprivation - 40 Years of Cardiovascular Research.
    B Ostadal, Z Drahota, M Hlavackova, P Ostadal.
      Experimental and clinical studies have clearly demonstrated significant sex differences in myocardial structure and function, both under physiological and pathological conditions. The best example are significant sex differences in the cardiac tolerance to ischemia/reperfusion injury: pre-menopausal adult female hearts are more resistant as compared to the male myocardium. The importance of these findings is supported by the fact that the number of studies dealing with this issue increased significantly in recent years. Detailed molecular and cellular mechanisms responsible for sex differences are yet to be elucidated; however, it has been stressed that the differences cannot be explained only by the effect of estrogens. In recent years, a promising new hypothesis has been developed, suggesting that mitochondria may play a significant role in the sex differences in cardiac tolerance to oxygen deprivation. However, one is clear already today: sex differences are so important that they should be taken into consideration in the clinical practice for the selection of the optimal diagnostic and therapeutic strategy in the treatment of ischemic heart disease. The present review attempts to summarize the progress in cardiovascular research on sex-related differences in cardiac tolerance to oxygen deprivation during the last 40 years, i.e. from the first experimental observation. Particular attention was paid to the sex-related differences of the normal heart, sex-dependent tolerance to ischemia-reperfusion injury, the role of hormones and, finally, to the possible role of cardiac mitochondria in the mechanism of sex-dependent differences in cardiac tolerance to ischemia/reperfusion injury. Key words: Female heart, Cardiac hypoxic tolerance, Ischemia-reperfusion injury, Sex differences.
  2. Tissue Barriers. 2024 Nov 25. 2431416
    Metabolic alterations of endothelial cells under transient and persistent hypoxia: study using a 3D microvessels-on-chip model.
    Kanchana Pandian, Anton Jan van Zonneveld, Amy Harms, Thomas Hankemeier.
      Numerous signaling pathways are activated during hypoxia to facilitate angiogenesis, promoting interactions among endothelial cells and initiating downstream signaling cascades. Although the pivotal role of the nitric oxide (NO) response pathway is well-established, the involvement of arginine-specific metabolism and bioactive lipid mechanisms in 3D flow-activated in vitro models remains less understood. In this study, we explored the levels of arginine-specific metabolites and bioactive lipids in human coronary artery endothelial cells (HCAECs) under both transient and persistent hypoxia. We compared targeted metabolite levels between a 2D static culture model and a 3D microvessels-on-chip model. Notably, we observed robust regulation of NO metabolites in both transient and persistent hypoxic conditions. In the 2D model under transient hypoxia, metabolic readouts of bioactive lipids revealed increased oxidative stress markers, a phenomenon not observed in the 3D microvessels. Furthermore, we made a novel discovery that the responses of bioactive lipids were regulated by hypoxia inducible factor-1α (HIF-1α) in the 2D cell culture model and partially by HIF-1α and flow-induced shear stress in the 3D microvessels. Immunostaining confirmed the HIF-1α-induced regulation under both hypoxic conditions. Real-time oxygen measurements in the 3D microvessels using an oxygen probe validated that oxygen levels were maintained in the 3D model. Overall, our findings underscore the critical regulatory roles of HIF-1α and shear stress in NO metabolites and bioactive lipids in both 2D and 3D cell culture models.
    Keywords:  3D microvessels-on-chip model; endothelial dysfunction; hypoxia; hypoxia inducible factor – 1 alpha; nitric oxide metabolites; signaling lipids
    DOI:  https://doi.org/10.1080/21688370.2024.2431416
  3. Behav Sci (Basel). 2024 Nov 12. pii: 1084. [Epub ahead of print]14(11):
    Effects of a Combined Method of Normobaric Hypoxia on the Repeated Sprint Ability Performance of a Nine-Time World Champion Triathlete: A Case Report.
    Adrian Gonzalez-Custodio, Carmen Crespo, Rafael Timón, Guillermo Olcina.
      Elite athletes are an under-represented population in scientific studies, and there are no works analysing the influence of hypoxia in elite triathletes. The aim of this study was to analyse the influence of different methods of normobaric hypoxia on repeated sprint ability (RSA) performance. This study was a case study with an elite triathlete who has won nine triathlon world championships. The study used a combination of different methods of normobaric hypoxia. The three methods combined were as follows: live high-train low interspersed; intermittent hypoxic training; and intermittent hypoxic exposure. This study analysed the influence of these methods on RSA performance in variables such as power output, saturation of muscular oxygen, heart rate and ventilatory variables (VO2 and VCO2). The triathlete was measured before the training protocol (PRE), just after (POST-D3) and 21 days after the end of the protocol (POST-D21). This type of protocol has shown that it can lead to an improvement in RSA performance in the number of sprints (PRE vs. POST-D3 vs. POST-D21: 19 vs. 24 vs. 28), power output (PRE 615 W vs. POST-D3 685 W vs. POST-D21 683W) and efficiency of the triathlete. This work may be useful in improving power output and repeated sprint ability for elite triathletes.
    Keywords:  case report; hypoxia; muscle oxygen saturation; repeated sprint ability; triathlon
    DOI:  https://doi.org/10.3390/bs14111084
  4. Int J Mol Sci. 2024 Nov 09. pii: 12051. [Epub ahead of print]25(22):
    Ginsenoside Rg1 Prevents and Treats Acute Pulmonary Injury Induced by High-Altitude Hypoxia.
    Junru Chen, Zhuo Zhang, Mingyue Huang, Jiayi Yan, Rong Gao, Jialu Cui, Yue Gao, Zengchun Ma.
      This study aimed to investigate the protective effects of ginsenoside Rg1 on high-altitude hypoxia-induced acute lung injury (ALI) and elucidated its molecular targets and related pathways, specifically its association with the fluid shear stress pathway. Using a combination of bioinformatics analysis and both in vivo and in vitro experiments, we assessed the role of ginsenoside Rg1 in mitigating physiological and biochemical disturbances induced by hypoxia. In the in vivo experiments, we measured arterial blood gas parameters, levels of inflammatory cells and cytokines, erythrocyte and platelet parameters, and conducted histological analysis in rats. The in vitro experiments utilized human pulmonary microvascular endothelial cells (HPMECs) and A549 cells to examine cell viability, intracellular reactive oxygen species (ROS) and Ca2⁺ levels, and mitochondrial function. The results of the in vivo experiments demonstrate that ginsenoside Rg1 significantly increased arterial blood oxygen partial pressure and saturation, elevated arterial blood glucose levels, and stabilized respiratory and metabolic functions in rats. It also reduced inflammatory cells and cytokines, such as tumor necrosis factor-α and interleukin-6, and improved erythrocyte and platelet abnormalities, supporting its protective role through the regulation of the fluid shear stress pathway. Histological and ultrastructural analyses revealed that Rg1 significantly protected lung tissue structure and organelles. In vitro experiments further confirmed that Rg1 improved cell viability in HPMEC and A549 cells under hypoxic conditions, decreased intracellular ROS and Ca2⁺ levels, and enhanced mitochondrial function. These findings collectively demonstrate that ginsenoside Rg1 exerts significant protective effects against high-altitude hypoxia-induced ALI by enhancing oxygen delivery and utilization, reducing inflammatory responses, and maintaining cellular metabolism and vascular function. Notably, the protective effects of Rg1 are closely associated with the regulation of the fluid shear stress pathway, suggesting its potential for treating high-altitude hypoxia-related diseases.
    Keywords:  acute lung injury; fluid shear stress; ginsenoside Rg1; high-altitude hypoxia; inflammation; mitochondrial function
    DOI:  https://doi.org/10.3390/ijms252212051
  5. Res Sq. 2024 Nov 19. pii: rs.3.rs-5349113. [Epub ahead of print]
    From Hypoxia to Buoyancy: Serotonin and Oxygen Deprivation Rewire Neutrophils.
    Luz P Blanco, Jorge Romo-Tena, Xinghao Wang, Yaima L Lightfoot, Mariana J Kaplan.
      Herein, we describe a method to purify higher buoyancy neutrophils in vitro after exposure of whole blood to brief hypoxia and reoxygenation in combination with platelet- derived serotonin. These higher buoyancy neutrophils display enhanced ability to form neutrophil extracellular traps and increment the tryptamine-protein adducts. Similar changes are identified in neutrophils isolated from patients with systemic lupus erythematosus. These results suggest that neutrophils may be rewired in tissues under conditions of hypoxia-reperfusion such as those seen in chronic inflammatory conditions.
    DOI:  https://doi.org/10.21203/rs.3.rs-5349113/v1
  6. World J Gastroenterol. 2024 Nov 28. 30(44): 4689-4696
    Hypoxia-related bioinformatic signatures associated with prognosis and tumor microenvironment of pancreatic cancer: Current status, concerns, and future perspectives.
    Dong-Ming Li, Xue-Yuan Cao, Jing Jiang.
      Pancreatic cancer (PC), a highly lethal tumor with nearly identical incidence and mortality rates, has become the sixth leading cause of cancer-related deaths. Hypoxia is an important malignant factor in PC, as it regulates angiogenesis, metabolic reprogramming, tumor progression, and metastasis. Disrupting the hypoxic microenvironment can enhance the efficacy of antitumor therapy and improve the prognosis of patients with PC. With the advent of bioinformatics, hypoxia-related PC models have emerged in recent years. They provide a reference for estimating the prognosis and immune microenvironment of patients with PC and identify potential biomarkers for targeting hypoxic microenvironment. However, these findings based on bioinformatic analysis may not be completely reliable without further experimental evidence and clinical cohort validation. The application of these models and biomarkers in clinical practice to predict survival time and develop anti hypoxic therapeutic strategies for patients with PC remains in its infancy. In this editorial, we review the current status of hypoxia-related prognostic models in PC, analyze their similarities and differences, discuss several existing challenges, and provide potential solutions and directions for further studies. This editorial will facilitate the optimization, validation, and determination of the molecular mechanisms of related models.
    Keywords:  Bioinformatics analysis; Hypoxia; Pancreatic cancer; Prognosis; Tumor microenvironment
    DOI:  https://doi.org/10.3748/wjg.v30.i44.4689
  7. High Alt Med Biol. 2024 Nov 27.
    Supplemental Oxygen on the Annie Smith Peck Expedition of 1903 to 6,367 m (20,892 ft) Mount Sorata (Illampu).
    Harvey V Lankford, Hannah Kimberley.
      Lankford, Harvey V, Hannah Kimberley. Supplemental Oxygen on the Annie Smith Peck Expedition of 1903 to 6,367 m (20,892 ft) Mount Sorata (Illampu). High Alt Med Biol. 00:00-00, 2024. The 1903 expedition to 6,367 m (20,892 ft) Mount Sorata (Illampu) in Bolivia that was conceived, organized, and led by American mountaineer Annie Smith Peck appears to have been the first to take a supplemental oxygen apparatus to a great mountain. The expedition did not have heavy cylinders of compressed oxygen or closed-circuit rebreathers with chemically generated oxygen but took an apparatus to produce oxygen on the mountain apparently by a 19th century heated chlorate chemical method. Oxygen was to be manufactured in camp, stored in rubber bags, and used with an open-circuit breathing set while climbing. The equipment was taken, but once in Bolivia, a late change in plans resulted in a summit attempt on 6,427 m (21,086 ft) Ancohuma rather than Illampu on the twin-peaked Sorata massif. The summit attempt ended prematurely at 4,700 m (15,350 ft), and the oxygen system was not used. The present paper reviews some of the supplemental oxygen options that were available in 1903 and examines the Sorata expedition, a little-known part of the early history of mountaineering oxygen use.
    Keywords:  Everest; Oxylithe; altitude; carbon dioxide; chlorate; closed-circuit; mountaineering; open-circuit; peroxide; rebreather; superoxide
    DOI:  https://doi.org/10.1089/ham.2024.0098
  8. Int J Mol Sci. 2024 Nov 19. pii: 12394. [Epub ahead of print]25(22):
    Genomic Insights into Tibetan Sheep Adaptation to Different Altitude Environments.
    Wentao Zhang, Chao Yuan, Xuejiao An, Tingting Guo, Caihong Wei, Zengkui Lu, Jianbin Liu.
      In recent years, research has gradually uncovered the mechanisms of animal adaptation to hypoxic conditions in different altitude environments, particularly at the genomic level. However, past genomic studies on high-altitude adaptation have often not delved deeply into the differences between varying altitude levels. This study conducted whole-genome sequencing on 60 Tibetan sheep (Medium Altitude Group (MA): 20 Tao sheep (TS) at 2887 m, High Altitude Group (HA): 20 OuLa sheep (OL) at 3501 m, and Ultra-High Altitude Group (UA): 20 AWang sheep (AW) at 4643 m) from different regions of the Tibetan Plateau in China to assess their responses under varying conditions. Population genetic structure analysis revealed that the three groups are genetically independent, but the TS and OL groups have experienced gene flow with other northern Chinese sheep due to geographical factors. Selection signal analysis identified FGF10, MMP14, SLC25A51, NDUFB8, ALAS1, PRMT1, PRMT5, and HIF1AN as genes associated with ultra-high-altitude hypoxia adaptation, while HMOX2, SEMA4G, SLC16A2, SLC22A17, and BCL2L2 were linked to high-altitude hypoxia adaptation. Functional analysis showed that ultra-high-altitude adaptation genes tend to influence physiological mechanisms directly affecting oxygen uptake, such as lung development, angiogenesis, and red blood cell formation. In contrast, high-altitude adaptation genes are more inclined to regulate mitochondrial DNA replication, iron homeostasis, and calcium signaling pathways to maintain cellular function. Additionally, the functions of shared genes further support the adaptive capacity of Tibetan sheep across a broad geographic range, indicating that these genes offer significant selective advantages in coping with oxygen scarcity. In summary, this study not only reveals the genetic basis of Tibetan sheep adaptation to different altitudinal conditions but also highlights the differences in gene regulation between ultra-high- and high-altitude adaptations. These findings offer new insights into the adaptive evolution of animals in extreme environments and provide a reference for exploring adaptation mechanisms in other species under hypoxic conditions.
    Keywords:  Tibetan sheep; high altitude; selection signature; ultra-high altitude; whole-genome resequencing
    DOI:  https://doi.org/10.3390/ijms252212394
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